Definition, Etiology, Prevention and Treatment of Peri-Implantitis a Review

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REVIEW Open Access Definition, etiology, prevention and treatment of peri-implantitis – a review Ralf Smeets1*, Anders Henningsen1, Ole Jung1, Max Heiland1, Christian Hammächer2 and Jamal M Stein3

Abstract Peri-implant inflammations represent serious diseases after dental implant treatment, which affect both the surrounding hard and soft tissue. Due to prevalence rates up to 56%, peri-implantitis can lead to the loss of the implant without multilateral prevention and therapy concepts. Specific continuous check-ups with evaluation and elimination of risk factors (e.g. smoking, systemic diseases and periodontitis) are effective precautions. In addition to aspects of osseointegration, type and structure of the implant surface are of importance. For the treatment of peri-implant disease various conservative and surgical approaches are available. Mucositis and moderate forms of peri-implantitis can obviously be treated effectively using conservative methods. These include the utilization of different manual ablations, laser-supported systems as well as photodynamic therapy, which may be extended by local or systemic antibiotics. It is possible to regain osseointegration. In cases with advanced peri-implantitis surgical therapies are more effective than conservative approaches. Depending on the configuration of the defects, resective surgery can be carried out for elimination of peri-implant lesions, whereas regenerative therapies may be applicable for defect filling. The cumulative interceptive supportive therapy (CIST) protocol serves as guidance for the treatment of the peri-implantitis. The aim of this review is to provide an overview about current data and to give advices regarding diagnosis, prevention and treatment of peri-implant disease for practitioners. Keywords: Peri-implantitis, Peri-implant disease, Review, Periodontal disease, Mucositis, Peri-implantitis therapy, Epidemiology, Etiology

Introduction on the pathogenesis, etiology, risk factors and prevention Dental implants have become an indispensable estab- of peri-implantitis, but also on actual recommendations in lished therapy in dentistry in order to replace missing treatment and therapy options. teeth in different clinical situations. Success rates of 82,9% after 16 years follow-up have been reported [1]. Under care and attention of indications, anatomical and Review intra-individual limiting factors, insertion of dental im- Definition und pathogenesis plants seems to represent a “safe” treatment option. In analogy to gingivitis and periodontitis affecting the Nevertheless, in the last decades increasing evidence periodontium of natural teeth, an inflammation and de- raised on the presence of peri-implant inflammations struction of soft and hard tissues surrounding dental im- representing one of the most frequent complications af- plants is termed as mucositis and peri-implantitis [2-4]. fecting both the surrounding soft and hard tissues which Thereby, transitions are often fluent and not clinically can lead to the loss of the implant. Therefore, strategies clearly separable [5]. for prevention and treatment of peri-implant disease Mucositis describes a bacteria-induced, reversible in- should be integrated in modern rehabilitation concepts in flammatory process of the peri-implant soft tissue with dentistry. The present review gives an updated overview reddening, swelling and bleeding on periodontal probing (Figure 1) [2-6]. These are typical signs, but they are sometimes not clearly visible. Furthermore, bleeding on * Correspondence: [email protected] probing (BOP) might be an indicator for peri-implant 1Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany disease, but sufficient evidence according to the predict- Full list of author information is available at the end of the article ive value of BOP is still lacking [7].

© 2014 Smeets et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Smeets et al. Head & Face Medicine 2014, 10:34 Page 2 of 13 http://www.head-face-med.com/content/10/1/34

through increased formation of inflammatory infiltrate, nitric oxide 1/3, VEGF, lymphocytes, leukocytes and Ki- 67 [10]. Besides, in analogy to periodontitis the level of matrix-metalloproteinases (MMP), such as MMP-8, is increased up to 971% in peri-implant lesions. The latter can be used for disgnostic purposes [11-13]. A differentiation of peri-implantitis to other inflammatory periodontal processes cannot be made on the basisofhumansalivabymarkerssuchasosteocalcin, tartrate-resistant acid phosphatase (TRAP), dickkopf- related protein-1 (DKK-1), osteoprotegerin (OPG) and cathepsin K (CatK) [9,14].

Etiology and epidemiology There are several reports on the prevalence of mucositis and peri-implantitis that differ between 5% and 63.4%. Figure 1 Peri-implantitis with increased probing depth (12 mm). This enormous range is mainly based on varying study designs and population sizes with different risk profiles and statistic profiles [5,15-18]. In contrast to mucositis, peri-implantitis is a progres- Zitzmann et al. quantified the incidence of the devel- sive and irreversible disease of implant-surrounding hard opment of peri-implantitis in patients with a history of and soft tissues and is accompanied with bone resorp- periodontitis almost six times higher than in patients tion, decreased osseointegration, increased pocket for- with no history of periodontal inflammation [3]. After mation and purulence [2-6]. Bleeding on probing, bone 10 years, 10% to 50% of the dental implants showed loss and deep probing depths may have other reasons signs of peri-implantitis [19,20]. Based on the Consensus than inflammation, e.g. too deep insertion of the implant Report of the Sixth European Workshop in Periodontol- [8]. Moreover, type and shape oft the implant, connec- ogy, Lindhe & Meyle reported an incidence of mucositis tion type, abutment and suprastructure material and the of up to 80% and of peri-implantitis between 28% and type of prosthetic suprastructure affect the peri-implant 56% [21]. soft and hard tissues [7]. However, the prevalence of peri-implant diseases, evalu- Depending on the configuration of the bony defect, ated recently by Mombelli et al., revealed peri-implantitis Schwarz et al. distinguished between an intraosseous in 20% of all implanted patients and in 10% of all inserted class I defect and a supra-alveolar class II defect in the implants. Although this percentage has to be interpreted crestal implant insertion area [5]. Spiekermann charac- with caution because of the variability of the analyzed terized the type of bone resorption into horizontal (class studies [7], it underlines the fact that bone remodeling I), key-shaped (class II), funnel- and gap-like (class III a, processes often result in marginal bone loss during the b) as well as horizontal-circular (class IV) forms [9]. first weeks after abutment connection which cannot be However, it is not possible to conclude progression and regarded as peri-implantitis. This led to the recommenda- prognosis criteria from these classifications. tion to take a radiograph after insertion of the suprastruc- On a microscopic and molecular level, striking diffe- ture and to consider it as a basis for any future assessment rences between peri-implant tissue and intact peri- of peri-implant bone loss. odontium can be determined (Table 1). Due to the Frequently, a spectrum of pathogenic germs can be de- reduced vascularization and parallel orientation of the tected such as Prevotella intermedia, Prevotella nigrescens, collagen fibres, peri-implant tissues are more susceptible Streptococcus constellatus, Aggregatibacter actinomycetem- for inflammatory disease than periodontal tissues. This comitans, Porphyromonas gingivalis, Treponema denticola phenomenon can be verified immunohistochemically and Tannerella forsythia [3,22]. Rams et al. revealed 71.7%

Table 1 Comparison of peri-implant mucosa with physiological periodontium [3,5] Peri-implant mucosa Physiological periodontium Desmosomes and hemidesmosomes of epithelium and junctional epithelium (biological width) are linked with the contact surface Direct bone-to-implant contact Anchoring system of root cementum, alveolar bone and desmodontic fibers Subepithelially more collagen fibers and less fibroblasts/vessels Subepithelially more fibroblasts and vessels Parallel collagen fibers in relation to implant surface Dentogingival, dentoperiostal, circular and transseptal fiber orientation Smeets et al. Head & Face Medicine 2014, 10:34 Page 3 of 13 http://www.head-face-med.com/content/10/1/34

resistance to at least one antimicrobial substance in a group study by Vervaeke et al. maxillary implants were at a sig- of 120 patients [22]. Peri-implantitisisapoly-microbialan- nificantly higher risk for peri-implant bone loss com- aerobic infection [23]. However, in contrast to periodontitis, pared to mandibular implants [31]. Bone augmented peri-implantitis lesions harborbacteriathatarenotpartof areas could not be determined as risk factors for implant the typical periodontopathic microbiota. In particular, failure or increased peri-implant disease [38]. Staphylococcus aureus appears to play a predominant role Across an observation period of 10 years in a group of for the development of a peri-implantitis. This bacterium patients with periodontitis, the previously eliminated shows an high affinity to titanium and has according to the bacterial strains of Aggregatibacter actinomycetemcomi- results of Salvi et al. a high positive (80%) and negative tans and Porphyromonas gingivalis could again be de- (90%) predictive value [24]. As another beneficial cause, tected in the oral mucosa [3]. Prevotella intermedia was, smooth implant surfaces in comparison to rough surfaces however, continuously evident. This indicates a niche can accelerate the peri-implant inflammation [10,17,25]. survival of bacteria after tooth extraction with recur- rence of the same microflora after a short period of time. Risk factors and prevention In particular, attention should be paid to the remaining Implant loss may occur as “early implant loss” up to one teeth with periodontitis as a potential source of infec- year after implant insertion and “delayed implant loss” tion. Therefore, the type of dentition (edentulous versus with a time period of more than one year after implant partially edentulous) may influence the colonization of insertion [3]. The following factors or circumstances peri-implant tissues with periodontal pathogens [38]. have been reported as risk factors for the development The impact of keratinized gingiva around dental im- of peri-implantitis [5,6,16,26-33]: plants has been controversially discussed, but most studies emphasize the importance of an adequate zone of Smoking with additional significantly higher risk of keratinized tissue surrounding implants [39-41]. The so complications in the presence of an positive called “cementitis” may be regarded as the most import- combined IL-1 genotype polymorphism. ant identifiable iatrogenic risk factor since its first de- History of periodontitis. scription by Wilson et al. in 2009 [42]. The latter group Lack of compliance and limited oral hygiene revealed that residual dental cement in a group of pa- (including missing checkups). tients with clinical or radiographic signs of peri-implant Systemic diseases (e.g. maladjusted diabetes mellitus, disease was present in 81% of the sites. After its removal, cardiovascular disease, immunosuppression). clinical signs were absent in 74% of the affected sites. Iatrogenic causes (e.g. “cementitis”). Korsch et al. found that the removal of cement remnants Soft tissue defects or poor-quality soft tissue at the led to a decrease of the inflammatory response by almost area of implantation (e.g. lack of keratinized gingiva). 60% [43]. Linkevizius et al. examined the manifestation History of one or more failures of implants. of peri-implantitis in a group of patients with present cement remnants. In those who had a history of periodon- Studies indicate smoking as the greatest identifiable titis, peri-implantitis was found in 100% of the patients, and most often cited risk factor for peri-implant disease whereas cement remnants in patients with no previous followed by a history of periodontitis. Both are related to periodontal disease ended up in 65% peri-implantitis higher prevalences of peri-implantitis [7]. The presence manifestations [30]. Another preventive arrangement re- of periodontitis or cigarette smoking increased the risk garding antibacterial precautions are internal connec- for peri-implantitis up to 4.7-fold as reported by tions with inward located microgap, which should be Wallowy et al. [6]. Moreover, smoking has been shown preferred. [6]. to be a predictor for implant failure [31]. In a recent Peri-implant probing is recommended to be carried meta-analysis smoking increased the annual rate of bone out carefully with a minimal probing force. However, the loss by 0.16 mm/year and represented the main systemic so-called platform switch (abutment is located horizon- risk factor [34]. The extent of osseointegration as well as tally between implant and crown) can complicate prob- the oral hygiene around dental implants was found to be ing and, thus, hide the true extension of peri-implantitis reduced among smokers [35]. It is commonly accepted [3,5,17,26,44]. Nevertheless, studies have indicated that that the outcome of almost all intraoral therapeutic pa- platform switch might be an important protective factor rameters are negatively affected by smoking although against peri-implant disease [45]. not in all previous studies a positive correlation between Implant loss can be differentiated on the basis of the peri-implantitis and tobacco smoking could be found following additional factors [3,5,6,46-49]: [36,37]. Evidence of predictors for implant success such as gender or age could not be found but for the jaw of Overloading of the implant, treatment (maxillary versus mandibular implants). In a Faults in material and techniques, Smeets et al. Head & Face Medicine 2014, 10:34 Page 4 of 13 http://www.head-face-med.com/content/10/1/34

Poor bone quality at the implant area, Therapy Systemic diseases and drug therapies, which inhibit The treatment of peri-implant infections comprises con- bone modulations according to “Wolff’slaw” (bone servative (non-surgical) and surgical approaches. De- density and strength increase with stress - and vice pending on the severity of the peri-implant disease versa). (mucositis, moderate or severe peri-implantitis) a non- surgical therapy alone might be sufficient or a step-wise Thus, implants of more than 10 mm length in square approach with a non-surgical therapy followed by a sur- thread design show higher success rates than shorter gical treatment may be necessary. implant lengths or shapes without thread or buttress thread [48,49]. Also rough implant surfaces of more Therapy of mucositis than 2 microns seem to feature better osseointegration One of the main aims of peri-implant therapy is to de- than smooth (<0.5 microns) or moderate surfaces (1–2 toxify the contaminated implant surface. In the presence microns) [17]. of peri-implant mucositis, non-surgical methods are ap- Development of strengths in the temporomandibular propriate and sufficient for detoxification. These include joint of more than 1300 Newton may shift the implants mechanical implant cleaning with titanium or plastic- in the first few months of healing up to 100 microns by curettes, ultrasonics or air polishing. Moreover, photo- presence of sagittal forces acting from an average of 50 dynamic therapy as well as local antiseptic medication Newton [46]. These average reference forces even in- (chlorhexidinglukonate, hydrogen peroxide, sodium per- crease to 87 Newton when articulation angles up to 60° carbonate, povidone-iodine) may support the antimicro- in horizontal axis. bial therapy. In addition to patient training sessions for optimal oral In two randomized clinical trials Heitz-Mayfield et al. hygiene, preventive strategies such as professional tooth and Hallström et al. were not able to prove any benefits and implant cleaning as well as individually continuous in reduction of pocket depth, plaque index or purulency peri-implant examinations (probing status) should be when adjuvant antimicrobial therapy (chlorhexidine and considered in order to prevent peri-implant diseases azithromycine) was used in addition to mechanical ther- (Table 2) [6]. Attention has to be paid, in particular, to apy only [50,51]. Reductions of the bleeding index were the reduction of the above-mentioned risk factors such explained by the general improvement of oral hygiene as heavy smoking or diabetes mellitus. with reference to the potential importance of guidelines As part of a holistic therapy, so-called reference pa- and treatment protocols [50-52]. The establishment of rameters (“hour zero”) and clearly determined control an adequate oral hygiene should, therefore, be consid- procedures have to be assessed with adequate docu- ered as key issue of the prevention of peri-implant infec- mentation. Radiographs should be taken pre-, intra- tions. Besides, a maintenance program with regular and post operatively in order to get information about evaluation of the peri-implant probing depths, support- the implantation site in which peri-implant inflamma- ive professional implant cleaning and oral hygiene train- tion will be detectable as brightening zones indicating ing should be integral part of every post-operative care increased bone resorption [6]. after implant insertion [2,6]. Prevention of peri-implant disease starts with a sufficient and structured planning including individual Therapy of peri-implantitis evaluation and minimization of risk factors (smoking, Most of the published strategies for peri-implantitis compliance, oral hygiene, periodontal disease, systemic therapy are mainly based on the treatments used for diseases), establishment of optimal soft and hard tissue teeth with periodontitis. The reason is that the way of conditions, the choice of the correct implant design bacterial colonization of dental and implant surfaces fol- followed by a maximally atraumatic approach and low similar principles, and it is commonly accepted that regular clinical examinations with a periodontal prob- the microbial biofilm plays an analogous role in the de- ing status. velopment of peri-implant inflammation [53]. For the

Table 2 Numbers of check-ups (cu) annually for different patient collectives cu = 1 cu = 2 cu > 3 Oral hygiene and hygienic ability of the implant well middle bad Smoking status / in history in presence Periodontitis, mucositis (with history) / / in presence Other risk factors / / e.g. systemic diseases, history of an non-successful implant insertion Smeets et al. Head & Face Medicine 2014, 10:34 Page 5 of 13 http://www.head-face-med.com/content/10/1/34

treatment of peri-implantitis, both conservative (non- surgival) as well as surgical therapies can be applied. Thereby, the surgical treatments can be done using resective or regenerative approaches [54-59].

Conservative therapy In addition to medication and manual treatment (e.g. with curettes, ultrasonic and air polishing systems) innovative techniques such as laser-supported and photodynamic therapy methods are recently described as conservative therapy options.

Manual treatment Basic manual treatment can be provided by teflon-, carbon-, plastic- and titanium curettes (Figure 2). Due to the fact that therapy with conventional curettes Figure 3 Conservative therapy – detoxification using an air is able to modify the implant surface and can roughen polishing device with glycin powder. the surface, it has been recommended that the material of the tip should be softer than titanium [60,61]. It is possible to reduce bleeding on probing scores by clean- hydroxylapatite > glycine > titanium dioxide > water and ing with piezoelectric scalers as well as with hand instru- air (control group) > phosphoric acid [64]. ments, and no differences have been found between An abrasive air polishing medium can modify the sur- these methods concerning reduction of bleeding on face of implants. After air powder treatment cell attach- probing, plaque index and probing depths after at least ment and cell viability still showed sufficient levels, but 6 months [62,63]. cell response was decreased compared with sterile sur- As to the above-mentioned methods, the efficacy of faces [64,65,67]. The extent of re-osseointegration of ti- ultrasonic curettage seems to underly the use of air pol- tanium implants after air polishing therapy has been ishing systems (Figure 3) [5,62,64-68]. Persson et al. and reported between 39% and 46% with increased clinical Renvert et al. experienced significantly lower numbers of implant attachment and pocket depth reduction [65]. bacteria with partial reduction of plaque and bleeding The occurrence of bleeding on probing, one of the quali- scores after mechanical curettage, while Schwarz et al. tative parameters in the presence of a peri-implantitis, reported 30%-40% less residual biofilm areas by using could be significantly reduced [67]. ultrasonic methods [5,63,66]. Depending on the surface topography of the implants, Louropoulou et al. recom- Drug therapy mend different therapeutic methods (Table 3). There are numerous in vitro and in vivo studies on the ap- The results of air polishing systems are depending on plication of medicaments as part of the treatment of mu- the used medium and are significantly better in the fol- cositis and peri-implantitis. However, due to differences in lowing order: hydroxylapatite/tricalcium phosphate > the design of all studies, comparison of these studies is dif- ficult. The following therapies can be distinguished:

Antiseptic rinses in relation to different parameters. Application of systemic and locally delivered antibiotics in relation to pocket depth or different parameters.

In a review by Javed et al., summarizing nine studies, systemic and local antibiotic applications (e.g. tetracycline, doxycycline, amoxicillin, metronidazole, minoxicycline hydrochloride, ciprofloxacin, sulfonamides + trimetho- prim) led to significant reductions of pocket depths in a period between one and six years [69]. Moura et al. noticed the same for resorbable doxicycline releasing – Figure 2 Conservative therapy example of the use of a nanospheres in local application over a period of carbone curette. 15 months [70]. Leonhardt et al. noticed an overall Smeets et al. Head & Face Medicine 2014, 10:34 Page 6 of 13 http://www.head-face-med.com/content/10/1/34

Table 3 Qualitative effectiveness (x: yes/o: no) of different cleaning methods depending on implant surface [68] Smooth surface Sandblasted and acid-etched surface (SLA) Plasma sprayed surface Rubber cap oo o Metalic curette, rotating titanium brush ox x Plastic curette oo o Ultrasonic systems with metalic tips x (polished) Ultrasonic systems with plastic tips ox x Air polishing xx x success rate of 58% when treating peri-implantitis with using a Poly-ε-Caprolacton/Alginat-ring [79]. Hou surgical debridement and the use of various antibiotics et al. incorporated fluorouracil into cylindrical poly-ε- and combinations of them (including clindamycin, caprolactone-implants of different diameters [80]. amoxicillin + metronidazole, tetracycline, ciprofloxa- Local or systemic antibiotics are an additional therapy cin) [71]. option. In combination with other conservative or surgi- Astasov-Frauenhoffer et al. were able to prove complete cal treatments it results in more efficient reductions of growth-inhibiting effects of amoxicillin and metronidazole clinical peri-implantitis symptoms [81]. Just administra- on Streptococcus sanguinis, Porphyromonas gingivalis and tion of antibiotics is no treatment option. Fusobacterum nucleatum apart from each other, but the combination was found to be more efficient than metro- Laser therapy nidazole alone [72]. Comparing local antibiotic therapy By means of a bactericide mode of action, CO2, Diode-, with photodynamic therapy, Bassetti et al. presented no Er:YAG- (erbium-doped: yttrium-aluminum-garnet) differences in reduction of pocket depths or reduction of and Er,Cr:YSGG- (erbium, chromium-doped: yttrium- the number of bacteria in the periodontal pockets [73]. scandium-gallium-garnet) lasers are used in the treatment Grapefruit juice, known as antioxidant, had only a bac- of peri-implant diseases with increasing frequency. Min- teriostatic effect against Streptococcus aureus [74]. But is imal absorption and reverberations must be ensured with has to be considered that depending on the type, bacteria the purpose to protect implant and tissue. Er:YAG and Er, demonstrate different high resistances against antibiotics Cr :YAG with a wavelength of 3 microns can reduce bio- (Table 4). Submucosal biofilm specimens were cultured films up to 90% but in contrast to most mechanical ther- from patients with peri-implantitis and after in vitro apies any biological compatibilities and cell stimulatory testing for susceptibility especially the combination of properties can’t be re-induced [5,82,83]. Treatment with a amoxicillin and metronidazole showed significant lower CO2 308 nm excimer laser, however, led mainly and effi- resistances (6.7%) [22]. ciently to satisfactory results in an anaerobic bacteria Application of chlorhexidine resulted in the reduction spectrum [84]. of pocket depths, a higher implant adhesion and general In comparison to mechanical methods (plastic curettes), weakening of inflammation measured by the level of the treatments with an Er:YAG laser led to significantly better inflammatory markers IL-1 beta, VEGF and PGE-2 in results in terms of bleeding at peri-implantitis. However, various studies [75-77]. Compared to minocycline both methods showed no significant differences in microsphere application repeated every three months changes of pocket depths, clinical attachment level, plaque [78], the treatment with 1% chlorhexidine gel resulted index and gingival recessions, although in both groups in significantly less reduced pocket depths after 12 months. these parameters were improved [85]. Concerning tissue engineering, Lan et al. demonstrated a Persson et al. examined the effectiveness of Er:YAG la- continuous release-kinetic of metronidazole for 30 days sers compared to an air polishing system in a randomized clinical trial with 42 patients over 6 months [86]. Table 4 Antibiotic resistance of Prevotella intermedia, Except for different reducing effects on specific bacteria Prevotella nigrescens and Streptococcus constellatus strains after one month (Er:YAG: Fusobacterium nuclea- (n = 120) [22] tum; air polishing system: Pseudomonas aeruginosa, Antibiotic Resistance Staphylococcus aureus and Peptostreptococcus anaerobius) Clindamycin 46,7% there were no long term-reducing effects shown after Amoxicillin 39,2% 6months.InarecentstudyMailoa et al. showed that Doxycycline 25% laser therapy resulted in similar reductions of probing depths when compared to other decontamination Metronidazole 21,7% methods [87]. Although there is only few data in com- Amoxicilin & metronidazol 6,7% parison to manual and surgical therapy, laser therapy as Smeets et al. Head & Face Medicine 2014, 10:34 Page 7 of 13 http://www.head-face-med.com/content/10/1/34

a treatment option has to be considered as an adjunct. Table 5 AKUT-protocol by Lang et al. [93] Further studies are needed to evaluate the profit of laser Stage Result Therapy therapy in peri-implantitis treatment. Pocket depth (PD) < No therapy 3 mm, no plaque or Photodynamic therapy bleeding Photodynamic therapy generates reactive oxygen species A PD < 3 mm, plaque and/ Mechanically cleaning, polishing, or bleeding on probing by multiplicity with help of a high-energy single-frequency oral hygienic instructions light (e.g. diode lasers) in combination with photosen- B PD 4-5 mm, radiologically Mechanically cleaning, polishing, sitizers (e.g. toluidine blue). In a wave length range of 580 no bone loss oral hygienic instructions plus local to 1400 nm and toluidine blue-concentrations between 10 antiinfective therapy (e.g. CHX) and 50 ug/ml, photodynamic therapy generates bactericide C PD > 5 mm, radiologically Mechanically cleaning, polishing, effects against aerobic and anaerobic bacteria (such as bone loss < 2 mm microbiological test, local and Aggregatibacter actinomycetemcomitans, Porphyromonas systemic antiinfective therapy gingivalis, Prevotella intermedia, Streptococcus mutans, D PD > 5 mm, radiologically Resective or regenerative surgery Enterococcus faecalis) [5,88,89]. The only prospective ran- bone loss > 2 mm domized clinical trail by Basseti et al. covered 12 months of follow-up. After manual debridement by titanium cu- The concept of Schmage follows the CIST-protocol but rec- rettes and glycine air powder treatment half of the patients ommends always mechanical and local disinfective treat- received adjunctive photodynamic therapy and the other ments in stage A and B. Intervention should be performed half received minocycline microspheres into implant if probing depths exceed 5 mm or are progressive as well as pockets. After 12 months, the number of periopathogenic under occurrence of local inflammation signs [94]. bacteria and level of IL-1β decreased significantly in both groups without significant differences between them [73]. Resective therapy In a study by Deppe et al. regarding to the effectiveness of In analogy to periodontitis, resective surgery has been phototherapy on a moderate and severe peri-implantitis, shown to be effective in reduction of BOP, probing depths both clinical attachment and bleeding index were signifi- and clinical signs of inflammation. The basic principles cantly reduced suggesting that severe cases still resulted in include the elimination the periimplant osseous defect bone resorption [90]. using ostectomy and osteoplasty as well as bacterial de- As a recommendation, photodynamic therapy has to be contamination (Figures 4 and 5). Additionally, smooth- considered as an additional treatment option. Due to the ening and polishing of the supracrestal implant surface fact that it is a relatively new approach, the data is rare (implantoplasty) may be applied. and there are no long-term-studies available. Further Serino et al. showed that in patients with active peri- evaluations and prospective clinical trials are needed for implant disease surgical pocket elimination and bone re- evaluation. contouring in combination with plaque control before and after surgery represents an effective treatment. Two Surgical therapy years after open reduction of inflammated peri-implant The surgical therapy combines the concepts of the soft tissue and osseous surgery 48% of the patients had already mentioned non-surgical therapy with those of no signs of peri-implantitis and 77% of the patients had resective and/or regenerative procedures. The indication for the appropriate treatment strategy has been demonstrated in patient studies leading to the development of the “cumulative interceptive supportive therapy (CIST)” concept [91-93]. In 2004 it was modified and called AKUT-concept by Lang et al. (Table 5) [93]. The basis of this concept is a regular recall of the implanted patient and repeated assessment of plaque, bleeding, suppuration, pockets and radiological evidence of bone loss. A further commonly accepted concept by Zitzmann et al. is referred to systematic periodontitis therapy. Du- ring the initial phase oral hygienic conditions have to be improved and mechanical cleaning and local antiinfective treatments are applied, if necessary. If non-surgical treatment fails, surgical intervention with open debridement Figure 4 Peri-implantitis with granulation tissue. and resective or regenerative therapy is recommended [3]. Smeets et al. Head & Face Medicine 2014, 10:34 Page 8 of 13 http://www.head-face-med.com/content/10/1/34

Figure 5 Peri-implantation 1 week after resective therapy. no implants with pocket depths ≥ 6 mm with bleeding and/or suppuration [56]. Figure 7 Regenerative therapie – defect fill with a xenograft In a radiographic study with 3 years follow-up, Romeo material (BioOss ®, Geistlich, Switzerland). et al. showed that the marginal bone loss after resective surgery with implantoplasty was significantly lower Regenerative approaches than after resective therapy only [55]. The group with Resective surgical therapy may result in re-osseointegration additional implantoplasty also had significantly lower in only minor superficial defects. From functional, esthetic probing pocket depths, probing attachment levels and and long-time-survival point of views, full regeneration and modified bleeding indices after 24 months [54]. re-osseointegration is aspired. In animal models it was pos- Adjuvant implant surface decontamination with anti- sible to regenerate experimentally induced defects using microbial substances led to an initially less anaerobic various graft materials and/or resorbable membranes fol- bacteria contamination, but did not improve the clinical lowing the principles of guided bone regeneration (GBR) outcome [75]. (Figures 6, 7, 8, 9 and 10). Resective surgical therapy for peri-implantitis is a rec- In a study by Hürzeler et al. in 1997 in dogs, there ommendable therapy option. Ostectomy and osteoplasty was no significant difference between the application combined with implantoplasty represent an effective of membranes only versus membranes in combination therapy to reduce or even stop peri-implantitis progression. Nevertheless, due to the increased postoperative recessions, this procedure is not suitable for every situ- ation, especially in highly esthetic sensitive areas.

Figure 8 Regenerative therapie – membrane application Figure 6 Regenerative therapie – defect after degranulation. (BioGide ®, Geistlich, Switzerland). Smeets et al. Head & Face Medicine 2014, 10:34 Page 9 of 13 http://www.head-face-med.com/content/10/1/34

a high variability in the amount of bone fill due to different investigation protocols and measurements [97-99] and not in all studies there was a benefit for these treatments compared to debridement alone [100-102]. The role of submerged healing in peri-implantitis has not been solved clearly. Although Singh et al. demonstrated in 1993 greater bone regeneration and re-osseointegration during submerged healing, Grunder et al. found no differences between either healing method [103,104]. Additionally, there are numerous studies regarding the treatment of peri-implantitis in humans under regenerative aspects. In a retrospective study of Lagervall et al. with 150 patients (382 implants) the most widely used operative intervention was the periodontal flap with osteoplasty (47%), followed by the use of bone replacement Figure 9 Preoperative radiograph of the peri-implant defect. materials (20%). A cumulative success rate of 69% was recorded for both procedures, which was significantly with bone grafts (canine demineralized freeze-dried lower in patients with risk factors such as smoking, peri- bone or hydroxyapatite) in terms of bone regeneration. odontal disease and poor oral hygiene [29]. Regarding to However, the combination resulted in a greater amount of a “regenerative” approach, autologous, allogenic and xeno- re-osseointegration [95]. No statistical differences in re- genic bone replacement materials are often used for aug- osseointegration could be demonstrated after treatment mentation in bone defects used with or without collagen with GBR using a e-PTFE reinforced membrane com- membrane. Allogenic and xenogenic grafts may be almost pared to sites without this membrane [96]. The treat- equivalent to autogenous material [105-107]. Schwarz ment resulted in 60–80% bone fill of the bony defect, et al. treated 22 patients randomly with access flap surgery but the absolute amount of re-osseointegration was and the application of nanocrystalline hydroxyapatite in small (between 0.1 - 0.6 mm). contrast to xenogenic bone material with collagen In contrast to debridement with surface decontamin- membrane. No significant differences were determined ation, in most of all animal studies regenerative methods between the groups, but 6 months after surgery both were reported as more efficient. In general, GBR alone treatments resulted in clinically relevant reductions in and bone fill alone have been shown to be more effective probing depths and gains of clinical attachment level than debridement alone regarding to bone regeneration [108]. Roos-Jansåker et al. came to similar results using and re-osseointegration. The results of studies using a a coralline xenograft [19]. In another study bovine- combination of membranes and bone graft materials derived xenogenic material was compared with au- were superior to those using membranes or bone grafts togenous bone as filling material for infracrestal defects. alone and tend to give the best results, However, there is The xenograft provided radiologically more bone fill and decreases in pocket depths, while bleeding on probing and suppuration were observed at both procedures [109]. In a prospective study, 36 cases of peri-implant bone loss were treated after local disinfection and removal of granulation tissue with a 1:1 mixture of autologous bone and a xenogenic bone graft. The result was a mean radiologically reduction of 3.5 mm from 5.1 mm one year after treatment with an average reduction of probing depths of 4 mm [59]. In a recent prospective case series a combined resective and regenerative approach including a bovine bone mineral and a collagen membrane infracrestally and implantoplasty supracrestally showed a significant peri-implant probing depth reduction and an increased radiographic defect fill after 12 months of follow- up [110]. In another study of Schwarz et al. defect cleaning with either Er:YAG laser or plastic curettes/cotton pellets Figure 10 Postoperative radiograph 12 months after with saline was combined with regenerative surgical proce- regenerative therapy. dures (xenogenic bone substitute and collagen membrane). Smeets et al. Head & Face Medicine 2014, 10:34 Page 10 of 13 http://www.head-face-med.com/content/10/1/34

Thereby, the clinical outcome did not differ according to Competing interests the chosen method of surface debridement [111]. The authors declare that they have no competing interests. In purpose of bone regeneration various approaches Authors’ contributions have been described with various success rates. There is The research has been carried out equally by RS, AH and OJ. JMS and MH a tendency that xenograft materials in combination with supervised and corrected the manuscript. CH provided and edited the a resorbable membranes might have advantages in terms photographs. All authors read and approved the final manuscript. of re-osseointegration. Nevertheless, because of the lack Author details of prospective randomized clinical studies there is no 1Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. 2Private evident data concerning the long-time stability of such 3 “ ” Practice, Schumacherstrasse 14, 52062 Aachen, Germany. Department of defect fillings . Conservative Dentistry, Periodontology and Preventive Dentistry, University Hospital Aachen, Pauwelsstr.30, 52074 Aachen, Germany.

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doi:10.1186/1746-160X-10-34 Cite this article as: Smeets et al.: Definition, etiology, prevention and treatment of peri-implantitis – a review. Head & Face Medicine 2014 10:34.

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